Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation

Yang, Peng; Ding, Guo-Bin; Li, Wen; Fu, Rong; Amin, Saima; Li, Zhuoyu

doi:10.1039/c8fo01161c

Cited by 42 publications

(44 citation statements)

References 40 publications

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“…In our study, we found that PB2 enhanced the effect of SORA on HCC both in vivo and in vitro by targeting PKM2. Emerging evidence has revealed that botanic flavonoids, including oroxylin A, tannic acid, and genistein, enhance the chemosensitivity to SORA [11, 48, 49]. Because PB2 is a nontoxic agent to L02 cells and mice, PB2 is a promising agent to act as a chemopreventive or chemotherapeutic medicine to treat HCC.…”

Section: Discussionmentioning

confidence: 99%

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

Jiao

et al. 2019

J Exp Clin Cancer Res

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Background The treatment for advanced primary hepatocellular carcinoma (HCC) is sorafenib (SORA), while HCC has become increasingly drug resistant with enhanced aerobic glycolysis. The present study aimed to examine the chemotherapeutic effects of a flavonoid proanthocyanidin B2 (PB2) on HCC. Methods Five kinds of HCC cell lines and LO2 were used to test the effect of PB2 on aerobic glycolysis. The proliferation, cell cycle, apoptosis and a xenograft mouse model were analyzed. Lentivirus overexpressed pyruvate kinase M2 (PKM2) or sh-PKM2 was used to verify the target of PB2. The detailed mechanism was investigated by immunofluorescence, co-immunoprecipitation, and western blotting. Results PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro. PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2. In addition, PKM2 inhibited the nuclear translocation of PKM2 and co-localization of PKM2/HIF-1α in the nucleus, leading to the inhibition of aerobic glycolysis. Co-treatment with PB2 was also effective in enhancing the chemosensitivity of SORA. Conclusions PB2 inhibited the expression and nuclear translocation of PKM2, therefore disrupting the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis and proliferation, and trigger apoptosis in HCC via HIF-1α-mediated transcription suppression. Electronic supplementary material The online version of this article (10.1186/s13046-019-1194-z) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

Jiao

et al. 2019

J Exp Clin Cancer Res

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“…This finally induces cell cycle arrest as described for HCT116 cells 38 , supported by our own observations. TA is thus considered a potential anticancer agent [39][40][41] , with additional ability to act as chemosensitizer 42 . The latter is a characteristic quite common for other polyphenols as well.…”

Section: Discussionmentioning

confidence: 99%

“…Apart from the therapeutic effect of TA, a recent study even proposed this substance as a promising pyruvate kinase isoenzyme M2 inhibitor for CRC prevention 39 . Still, clinical evidence of dietary polyphenols as chemopreventive compounds is scarce and at least partially attributable to the fact that TA concentrations in the gastrointestinal tract are hardly measurable and backtracked to mediate a direct tumor growth inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

Streptococcus gallolyticus abrogates anti-carcinogenic properties of tannic acid on low-passage colorectal carcinomas

Oehmcke-Hecht

Mandl

Naatz

et al. 2020

Sci Rep

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the tannase-producing Gram-positive bacterial species Streptococcus gallolyticus subsp. gallolyticus (Sgg) is an opportunistic pathogen of the human gut and strongly associated with colorectal cancer (cRc). A unique feature of Sgg is its ability to degrade tannic acids (tA). tA constitute an important part of the human diet with known anti-tumorigenic properties. Here, we examined whether Sgg is able to protect tumor cells from the toxic effect of TA and thus drive tumorigenesis indirectly. Human CRC cell lines (n = 8) were treated with increasing concentrations of TA. We confirmed the cytotoxic activity of TA in a dose-dependent manner. In virtually all cell lines, viability decreased significantly (>60% inhibition). Moreover, pyrogallol, the degradation product of TA, had no effect on the tested cell lines. This suggests a specific effect of TA. Cytotoxicity was due to necrosis and induction of senescence in residual cells. finally, when tA was degraded by Sgg, the cytotoxic effect could be abolished. Tumor cells even responded with boosted cell proliferation, highlighting the impact of Sgg on cRc progression. We here provide another piece of evidence for the active interplay between Sgg and cancer preventive components. these data will help to move forward in designing concepts for therapeutic and eventually also prophylactic approaches to combat gastrointestinal malignancies.

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“…The detailed methods of cell culture were described in our previous studies 31 . Cell proliferation was detected by MTT assay and EdU assay 32 . A clonogenic assay was carried out as previously reported 32 .…”

Section: Methodsmentioning

confidence: 99%

Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3

Yang

et al. 2019

Cell Death Dis

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Colorectal cancer (CRC) is a common malignant gastrointestinal tumor with high mortality worldwide. Drug resistance and cytotoxicity to normal cells are the main causes of chemotherapeutic treatment failure in CRC. Therefore, extracting the bioactive compounds from natural products with anti-carcinogenic activity and minimal side-effects is a promising strategy against CRC. The present study aims to evaluate the anti-carcinogenic properties of avenanthramides (AVNs) extracted from oats bran and clarify the underlying molecular mechanisms. We demonstrated that AVNs treatment suppressed mitochondrial bioenergetic generation, resulting in mitochondrial swelling and increased reactive oxygen species (ROS) production. Further study indicated that AVNs treatment significantly reduced DDX3 expression, an oncogenic RNA helicase highly expressed in human CRC tissues. DDX3 overexpression reversed the ROS-mediated CRC apoptosis induced by AVNs. Of note, we identified Avenanthramide A (AVN A) as the effective ingredient in AVNs extracts. AVN A blocked the ATPase activity of DDX3 and induced its degradation by directly binding to the Arg287 and Arg294 residues in DDX3. In conclusion, these innovative findings highlight that AVNs extracts, in particular its bioactive compound AVN A may crack the current hurdles in the way of CRC treatment.

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Tannic acid directly targets pyruvate kinase isoenzyme M2 to attenuate colon cancer cell proliferation

Cited by 42 publications

References 40 publications

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma

Streptococcus gallolyticus abrogates anti-carcinogenic properties of tannic acid on low-passage colorectal carcinomas

Avenanthramide A triggers potent ROS-mediated anti-tumor effects in colorectal cancer by directly targeting DDX3

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