Kaempferol suppresses bladder cancer tumor growth by inhibiting cell proliferation and inducing apoptosis

Abstract

The effects of the flavonoid compound, kaempferol, which is an inhibitor of cancer cell proliferation and an inducer of cell apoptosis have been shown in various cancers, including lung, pancreatic, and ovarian, but its effect has never been studied in bladder cancer. Here, we investigated the effects of kaempferol on bladder cancer using multiple in vitro cell lines and in vivo mice studies. The MTT assay results on various bladder cancer cell lines showed that kaempferol enhanced bladder cancer cell cytotoxicity. In contrast, when analyzed by the flow cytometric analysis, DNA ladder experiment, and TUNEL assay, kaempferol significantly was shown to induce apoptosis and cell cycle arrest. These in vitro results were confirmed in in vivo mice studies using subcutaneous xenografted mouse models. Consistent with the in vitro results, we found that treating mice with kaempferol significant suppression in tumor growth compared to the control group mice. Tumor tissue staining results showed decreased expressions of the growth related markers, yet increased expressions in apoptosis markers in the kaempferol treated group mice tissues compared to the control group mice. In addition, our in vitro and in vivo data showed kaempferol can also inhibit bladder cancer invasion and metastasis. Further mechanism dissection studies showed that significant down-regulation of the c-Met/p38 signaling pathway is responsible for the kaempferol mediated cell proliferation inhibition. All these findings suggest kaempferol might be an effective and novel chemotherapeutic drug to apply for the future therapeutic agent to combat bladder cancer.

Kaempferol Modulates DNA Methylation and Downregulates DNMT3B in Bladder Cancer

“…Kae was reported to be an anti-tumor reagent against many cancers, such as breast cancer, pancreatic cancer, prostate cancer, and lung cancer [9-12]. Previously, we found that Kae could suppress bladder cancer by inducing apoptosis both in vitro and in vivo [13, 14]. These data highlight that this compound may be a new candidate for the prevention and treatment of bladder cancer.…”

Screening for quality indicators and phenolic compounds of biotechnological interest in honey samples from six species of stingless bees (Hymenoptera: Apidae)

“…Luteolin is known to promote cell death by apoptosis and preservation of normal cells and also possesses significant anticancer properties (Chen & Chen, 2013;Dang et al, 2015;Zheng et al, 2014). Its presence in honey produced by Melipona q. anthidoides and Melipona mandacaia might attribute cell protecting properties.…”

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…It promotes apoptosis of HT-29 human colon cancer cells through activating cell surface death receptors and the mitochondrial pathway (72). In a recent paper, it was revealed that kaemperol attenuates the growth of 5637 and T24 human bladder cancer cells by inhibition of the c-Met/p38 MAPK signaling pathway in vitro and in vivo (73). The antitumor activity of kaempferol also has been shown in OVCAR-3 and A2780/CP70 human ovarian cancer cell lines, it suppresses expression of VEGF and angiogenesis by inhibiting the ERK-NF-κB pathway (74).…”