A marked decrease in human cancers, including breast cancer, bone cancer, and cervical cancer, has been linked to the consumption of vegetable and fruit, and the corresponding chemoprotective effect has been associated with the presence of several active molecules, such as kaempferol. Kaempferol is a major flavonoid aglycone found in many natural products, such as beans, bee pollen, broccoli, cabbage, capers, cauliflower, chia seeds, chives, cumin, moringa leaves, endive, fennel, and garlic. Kaempferol displays several pharmacological properties, among them antimicrobial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and antidiabetic activities, and is being applied in cancer chemotherapy. Specifically, kaempferol-rich food has been linked to a decrease in the risk of developing some types of cancers, including skin, liver, and colon. The mechanisms of action include apoptosis, cell cycle arrest at the G2/M phase, downregulation of epithelial-mesenchymal transition (EMT)-related markers, and phosphoinositide 3-kinase/protein kinase B signaling pathways. In this sense, this article reviews data from experimental studies that investigated the links between kaempferol and kaempferol-rich food intake and cancer prevention. Even though growing evidence supports the use of kaempferol for cancer prevention, further preclinical and clinical investigations using kaempferol or kaempferol-rich foods are of pivotal importance before any public health recommendation or formulation using kaempferol.

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Kaempferol: A Key Emphasis to Its Anticancer Potential

Kaempferol (kae) and its glycosides are widely distributed in nature and show multiple bioactivities, yet few reports have compared them. In this paper, we report the antitumor, antioxidant and anti-inflammatory activity differences of kae, kae-7-O-glucoside (kae-7-O-glu), kae-3-O-rhamnoside (kae-3-O-rha) and kae-3-O-rutinoside (kae-3-O-rut). Kae showed the highest antiproliferation effect on the human hepatoma cell line HepG2, mouse colon cancer cell line CT26 and mouse melanoma cell line B16F1. Kae also significantly inhibited AKT phosphorylation and cleaved caspase-9, caspase-7, caspase-3 and PARP in HepG2 cells. A kae-induced increase in DPPH and ABTS radical scavenging activity, inhibition of concanavalin A (Con A)-induced activation of T cell proliferation and NO or ROS production in LPS-induced RAW 264.7 macrophage cells were also seen. Kae glycosides were used to produce kae via environment-friendly enzymatic hydrolysis. Kae-7-O-glu and kae-3-O-rut were hydrolyzed to kae by β-glucosidase and/or α-L-rhamnosidase. This paper demonstrates the application of enzymatic catalysis to obtain highly biologically active kae. This work provides a novel and efficient preparation of high-value flavone-related products.

/pdf/antitumor-antioxidant-and-anti-inflammatory-activities-of-3tl9uu4ksl.pdf

Antitumor, antioxidant and anti-inflammatory activities of kaempferol and its corresponding glycosides and the enzymatic preparation of kaempferol.

Kaempferol, which is isolated from several natural plants, is a polyphenol belonging to the subgroup of flavonoids. Kaempferol exhibits various pharmacological activities, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. In this study, kaempferol can significantly inhibit the invasion and migration of 786-O renal cell carcinoma (RCC) without cytotoxicity. We examined the potential mechanisms underlying its anti-invasive activities on 786-O RCC cells. Western blot was performed, and the results showed that kaempferol attenuates the manifestation of metalloproteinase-2 (MMP-2) protein and activity. The inhibitive effect of kaempferol on MMP-2 may be attributed to the downregulation of phosphorylation of Akt and focal adhesion kinase (FAK). By examining the SCID mice model, we found that kaempferol can safely inhibit the metastasis of the 786-O RCC cells into the lungs by about 87.4% as compared to vehicle treated control animals. In addition, the lung tumor masses of mice pretreated with 2-10 mg/kg kaempferol were reduced about twofold to fourfold. These data suggested that kaempferol can play a promising role in tumor prevention and cancer metastasis inhibition.

/pdf/kaempferol-inhibits-the-invasion-and-migration-of-renal-46w67xv5jk.pdf

Kaempferol Inhibits the Invasion and Migration of Renal Cancer Cells through the Downregulation of AKT and FAK Pathways.

Kaempferol is a widely distributed dietary flavonoid. Epidemiological studies have demonstrated kaempferol consumption lowers the risk of ovarian cancer. Our previous research proved that kaempferol suppresses human ovarian cancer cells by inhibiting tumor angiogenesis. However, the effects of kaempferol on the cell cycle and extrinsic apoptosis of ovarian cancer cells have not yet been studied. In the present study, we demonstrated that kaempferol induced G2/M cell cycle arrest via the Chk2/Cdc25C/Cdc2 pathway and Chk2/p21/Cdc2 pathway in human ovarian cancer A2780/CP70 cells. Chk2 was not responsible for kaempferol-induced apoptosis and up-regulation of p53. Kaempferol stimulated extrinsic apoptosis via death receptors/FADD/Caspase-8 pathway. Our study suggested that Chk2 and death receptors played important roles in the anticancer activity of kaempferol in A2780/CP70 cells. These findings provide more evidence of the anti-ovarian cancer properties of kaempferol and suggest that kaempferol could be a potential candidate for ovarian cancer adjuvant therapy.

https://www.mdpi.com/1420-3049/23/5/1095/pdf

Kaempferol Induces G2/M Cell Cycle Arrest via Checkpoint Kinase 2 and Promotes Apoptosis via Death Receptors in Human Ovarian Carcinoma A2780/CP70 Cells

Overexpression of HIF-1a could partially protect K562 cells from 1,4-benzoquinone induced toxicity by inhibiting ROS, apoptosis and enhancing glycolysis.

The effect of kaempferol (3,5,7,4-tetrahydroxyflavone), a flavonoid compound that was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G2-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clones stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity and activation of the ATM/ATR-Chk1/Chk2 pathway, activating the phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), with resultant G2- arrest of the cell cycle. Under these conditions, apoptotic events, including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δψm) loss, activation of caspase-9, -8, and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G1 cells, were induced without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G2-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA-damage-mediated G2-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G2-checkpoint activation, which caused not only G2-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondriadependent apoptotic events, including Bak and PUMA upregulation, Bak activation, Δpsim loss, and caspase cascade activation.

Kaempferol Activates G₂-Checkpoint of the Cell Cycle Resulting in G₂-Arrest and Mitochondria-Dependent Apoptosis in Human Acute Leukemia Jurkat T Cells.

Ancestral ritual food of Korean jongka: Historical changes of the table setting

본 연구에서는 소비자들이 밀키트 선택 시 중요하게 생각하는 요인과 만족도를 조사하기 위해, 수도권에 거주하는 30∼49세 연령의 370명을 대상으로 온라인 설문조사를 실시하였다. 연구 결과, 조사 대상자의 밀키트 제품 이용 관련 사항 중 구매 횟수는 ‘주 1∼2회’가 143명(38.6%)으로 가장 높은 비율을 차지하였고, 월평균 구매비용은 ‘2∼5만 원 미만’이 141명(38.1%)으로 가장 높은 비율로 나타났다. 구매하는 장소는 ‘대형마트’가 198명(53.5%)으로 가장 높았고, 다음으로 ‘온라인 쇼핑몰’이 68명(18.4%)으로 높게 나타나, 할인마트나 편의점에서 구매하는 빈도가 높은 HMR 제품과는 차이를 보였다(Lee SM 등 2019). 새벽배송 서비스 도입, 상대적으로 저렴한 가격의 제품 등의 이유로 온라인 쇼핑몰에서 구입하는 소비자가 증가하고 있는 것으로 사료된다. 밀키트 제품의 선택속성에 대한 중요도-만족도 분석에서는 ‘친환경 식재료 사용’을 제외한 나머지 항목에서 중요도와 만족도 사이에 유의적 차이가 있었다. 밀키트 제품 구매 시 중요하게 생각하는 항목은 ‘위생(4.54)’, ‘품질(4.35)’, ‘맛(4.34)’ 등 순이었으며, 만족도는 ‘조리간편성(4.04)’, ‘구매용이성(3.89)’, ‘맛(3.81)’ 등이 높았다. 밀키트 제품의 선택속성에 대한 IPA 격자모형을 살펴보면 중요도는 높고, 만족도가 낮아 집중적으로 개선이 필요한 제 2사분면에는 ‘가격’, ‘포장단위(양)’ 항목이 속했다. 이러한 결과를 통해 제품의 합리적인 ‘가격’과 적합한 ‘포장단위(양)’를 설정하는 것이 제품 개발 시 우선적으로 고려될 사항인 것을 확인할 수 있었다. 왜냐하면 밀키트 제품의 경우, 대부분 완전히 조리되지 않고 손질된 신선재료와 반조리된 가공식품들이 결합되어 있기 때문에 일반적인 가정간편식보다 가격이 높은 경향을 보인다. 따라서 향후 밀키트 개발 업계는 제품의 품질은 유지하면서 사용하는 재료의 원가를 낮출 수 있는 방안을 마련하는 것이 중요하며, 가족 구성원의 감소 및 혼밥족 증가 등으로 변화되어 가는 소비자 식사 문화를 고려하여 밀키트 제품의 포장단위를 줄이거나 다양화하는 방안을 모색하는 것도 필요할 것으로 생각된다. 이와 더불어 밀키트 제품을 포함해 식품포장에 많이 사용되고 있는 플라스틱이나 비닐 등 1회용 포장지의 사용을 줄이기 위해, 포장 최소화 및 친환경 포장재 도입 등 환경을 고려한 포장방법에 대한 추가적인 연구가 필요할 것으로 사료된다. 밀키트는 현재 내식적 외식(가정에서 먹는 외식, Eatingout of Home)이면서 가정간편식(HMR)의 범주에 포함되며, 최근 가정식 열풍과 더불어 시간과 능률을 중시하는 현대인들의 경향을 반영한 반 조리된 식품이다. 현재까지의 밀키트와 관련된 여러 업체들의 시장 진입 및 제품 다양화 진행 속도를 살펴보았을 때, 밀키트 제품의 소비는 증가될 것으로 전망된다. 향후, 밀키트 시장의 안정적 성장을 위해서는 철저한 관리를 통한 ‘위생’ 강화로 소비자 신뢰성을 확보하는 노력이 필요할 것으로 생각된다. 또한, 밀키트 등 가정간편식으로 가정식을 대체하는 소비자가 증가하는 만큼, ‘맛’이나 ‘편의성’에만 집중하지 않고 ‘영양’에 대해 중요하게 인식할 필요가 있을 것으로 사료된다. 이러한 관리 체계와 노력하에 품질과 영양이 고려되면서 소비자들이 선호할 수 있는 다양한 밀키트 제품 개발이 이루어지길 기대해 본다.

Importance-Performance Analysis Regarding Selective Attribution of Meal-Kit Products

Exposure of Jurkat T cell clone (J/Neo cells) to acacetin (5,7-dihydroxy-4'-methoxyflavone), which is present in barnyard millet (Echinochloa esculenta (A. Braun)) grains, caused cytotoxicity, enhancement of apoptotic sub-G1 rate, Bak activation, loss of mitochondrial membrane potential (Δψ), activation of caspase-9 and caspase-3, degradation of poly(ADP-ribose) polymerase, and FITC-Annexin V-stainable phosphatidylserine exposure on the external surface of the cytoplasmic membrane without accompanying necrosis. These apoptotic responses were abrogated in Jurkat T cell clone (J/Bcl-xL) overexpressing Bcl-xL. Under the same conditions, cellular autophagic responses, including suppression of the Akt-mTOR pathway and p62/SQSTM1 down-regulation, were commonly detected in J/Neo and J/Bcl-xL cells; however, formation of acridine orange-stainable acidic vascular organelles, LC3-I/II conversion, and Beclin-1 phosphorylation (Ser-15) were detected only in J/Neo cells. Correspondingly, concomitant treatment with the autophagy inhibitor (3-methyladenine or LY294002) appeared to enhance acacetin-induced apoptotic responses, such as Bak activation, Δψ loss, activation of caspase-9 and caspase-3, and apoptotic sub-G1 accumulation. This indicated that acacetin could induce apoptosis and cytoprotective autophagy in Jurkat T cells simultaneously. Together, these results demonstrate that acacetin induces not only apoptotic cell death via activation of Bak, loss of Δψ, and activation of the mitochondrial caspase cascade, but also cytoprotective autophagy resulting from suppression of the Akt-mTOR pathway. Furthermore, pharmacologic inhibition of the autophagy pathway augments the activation of Bak and resultant mitochondrial damage-mediated apoptosis in Jurkat T cells.

Young Yun

Papers

Kaempferol Activates G₂-Checkpoint of the Cell Cycle Resulting in G₂-Arrest and Mitochondria-Dependent Apoptosis in Human Acute Leukemia Jurkat T Cells.

Ancestral ritual food of Korean jongka: Historical changes of the table setting

Importance-Performance Analysis Regarding Selective Attribution of Meal-Kit Products

Pharmacologic Inhibition of Autophagy Sensitizes Human Acute Leukemia Jurkat T Cells to Acacetin-Induced Apoptosis.

Ssam food recipe: A case study on jongka ancestral ritual food