Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin

Jandial, Danielle; Krill, Lauren; Chen, Lixia; Wu, Chunli; Yu, Ke; Xie, Jun; Hoang, Bang H.; Zi, Xiaolin

doi:10.20944/preprints201701.0098.v1

Cited by 13 publications

(4 citation statements)

References 41 publications

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“…The antiproliferative activity of chalcones is closely linked to cell cycle blockade and subsequent induction of apoptosis [ 171 ]. Tumor cell transformation, which may be the keystone for the development of cancer, may cause cells to be unresponsive to regulatory mechanisms and begin to divide uncontrollably.…”

Section: Cell Cycle and Tubulins As A Target Of Chalconesmentioning

confidence: 99%

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Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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Although great progress has been made in the treatment of cancer, the search for new promising molecules with antitumor activity is still one of the greatest challenges in the fight against cancer due to the increasing number of new cases each year. Chalcones (1,3-diphenyl-2-propen-1-one), the precursors of flavonoid synthesis in higher plants, possess a wide spectrum of biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer. A plethora of molecular mechanisms of action have been documented, including induction of apoptosis, autophagy, or other types of cell death, cell cycle changes, and modulation of several signaling pathways associated with cell survival or death. In addition, blockade of several steps of angiogenesis and proteasome inhibition has also been documented. This review summarizes the basic molecular mechanisms related to the antiproliferative effects of chalcones, focusing on research articles from the years January 2015–February 2021.

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Section: Cell Cycle and Tubulins As A Target Of Chalconesmentioning

confidence: 99%

“…In addition, several other natural chalcones have been shown to cause G2/M arrest via suppression of cyclin levels or inhibition of CdKs activity including ISL [ 175 ], flavokawain A [ 171 ], XNT [ 57 ], FKB [ 176 ], CAR [ 177 ], butein [ 150 ], and many others.…”

Section: Cell Cycle and Tubulins As A Target Of Chalconesmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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“…G2/M cell cycle arrest is one of the key mechanisms employed by many cytotoxic drugs to inhibit the growth of cancer cells (Shapiro and Harper 1999). Recent literature suggested that cytotoxic drugs including Xerophilusin B and Flavokwain induce G2/M phase arrest in cancer cell lines (Yao et al 2015;Jandial et al 2017). To bring apoptotic death in the cancer cell a proper transmission of signals is essential but in cancer cells, the signalling mechanism is impaired and death is halted (Evan et al 2001).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the anticancer activity of enzymatically synthesized Baccatin III: an intermediate precursor of Taxol®

et al. 2020

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Baccatin III is an important precursor for the synthesis of clinically important anticancer drug Taxol. Previously, we have characterized a key enzyme of 10-deacetylbaccatin III-10-β-O-acetyltransferase (DBAT) which catalyses the 10-deacetylbaccatin III into baccatin III in taxol biosynthesis. Here, in the present study, we have evaluated and compared the cytotoxic properties of the enzymatically synthesized baccatin III (ESB III) with standard baccatin III in different human cancer cell lines, namely human cervical cancer (HeLa), human lung cancer (A549), human skin cancer (A431) and human liver cancer cells (HepG2). Among the various cancer lines tested, HeLa was more susceptible to ESB III with IC 50 of 4.30 µM while IC 50 values for A549, A431 and HepG2 ranged from 4 to 7.81 µM. Further, it showed G2/M phase cell cycle arrest, production of reactive oxygen species and depolarised mitochondrial membrane potential. In addition, annexin V-FITC staining was performed which showed the apoptotic cell death of HeLa cells, when treated with ESB III. Hence, ESB III was capable to show anticancer activities by inducing apoptotic cell death which could further be used for the semisynthesis of taxol in future.

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“…Flavokawain A (FKA), which is a novel chalcone from kava plant, can induce G2/M arrest and inhibit invasion and metastasis in several types of cancer [8][9][10]. In our previous study, we utilized the national medical products administration (NMPA) approved sodium aescinate (Aes) to stabilize hydrophobic PTX and FKA to form polymer-free PTX-A nanoparticles (NPs) and FKA-A NPs.…”

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confidence: 99%

FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway

Wang

Liu

et al. 2022

Fundamemntal Clinical Pharma

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Recurrence and distant metastasis after paclitaxel (PTX)‐based chemotherapy in ovarian cancer (OC) patients remains a clinical obstacle. Flavokawain A (FKA) is a novel chalcone from kava plant that can induce G2/M arrest and inhibit invasion and metastasis in different tumor cells. In this study, we examined the effects and the molecular mechanism of sodium aescinate (Aes)‐stabilized nanoparticles FKA‐A NPs in enhancing the efficacy of PTX‐A NPs in vitro and in vivo. We showed that FKA‐A NPs combined with PTX‐A NPs notably inhibited the proliferation and migration and reduced the expression of EMT‐related markers in OCs. YAP nuclear translocation and its downstream signaling pathway were remarkably activated after PTX‐A NPs treatment in OCs. FKA‐A NPs obviously inhibited YAP nuclear translocation and reduced the transcriptional activity of YAP target genes. Simultaneously, FKA‐A NPs dose and time dependently inhibited Skp2 expression in A2780 and Skov3 cells. In contrast, overexpression of Skp2 significantly attenuated the inhibition of FKA‐A NPs on YAP nuclear translocation. In OC homograft mice, treatment with FKA‐A NPs and PTX‐A NPs significantly suppressed the growth of homograft tumor compared with PTX‐A NPs but did not decrease mice's body weight. In summary, we demonstrate that FKA‐A NPs enhance the efficacy of PTX‐A NPs against OCs in vitro and in vivo via reducing Skp2 expression, thus suppressing YAP nuclear translocation and activity of its target genes.

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Induction of G2M Arrest by Flavokawain A, A Kava Chalcone, Increases the Responsiveness of HER2 Overexpressing Breast Cancer Cells to Herceptin

Cited by 13 publications

References 41 publications

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Evaluation of the anticancer activity of enzymatically synthesized Baccatin III: an intermediate precursor of Taxol®

FKA‐A NPs enhances PTX‐A NPs efficacy to suppress ovarian cancer via regulating Skp2/YAP pathway

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