2. Academic Validation
  3. Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo

Synergistic Combination of Luteolin and Asiatic Acid on Cervical Cancer In Vitro and In Vivo

  • Cancers (Basel). 2023 Jan 16;15(2):548. doi: 10.3390/cancers15020548.
Ya-Hui Chen 1 2,  Jyun-Xue Wu 1,  Shun-Fa Yang 2 3,  Yi-Hsuan Hsiao 1 2 4 5 6 7
Affiliations

Affiliations

  • 1 Women's Health Research Laboratory, Changhua Christian Hospital, Changhua 50006, Taiwan.
  • 2 Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • 3 Department of Medical Research, Chung Shan Medical University Hospital, Taichung 40201, Taiwan.
  • 4 Department of Obstetrics and Gynecology, Changhua Christian Hospital, Changhua 50006, Taiwan.
  • 5 School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
  • 6 College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan.
  • 7 College of Medicine, National Chung Hsing University, Taichung 40227, Taiwan.
PMID: 36672499 DOI: 10.3390/cancers15020548
Abstract

Cervical Cancer is an important issue globally because it is the second most common gynecological malignant tumor and conventional treatment effects have been shown to be limited. Lut and AsA are plant-derived natural flavonoid and triterpenoid products that have exhibited Anticancer activities and can modulate various signaling pathways. Thus, the aim of the present study was to evaluate whether Lut combined with AsA could enhance the Anticancer effect to inhibit cervical Cancer cell proliferation and examine the underlying molecular mechanisms in vitro and in vivo. The results of a CCK-8 assay showed that Lut combined with AsA more effectively inhibited the proliferation of CaSki and HeLa cells than Lut or AsA treatment alone. Lut combined with AsA caused Apoptosis induction and sub-G1-phase arrest in CaSki and HeLa cells, as confirmed by flow cytometry, mitoROS analysis, antioxidant activity measurement and western blot assay. In addition, Lut combined with AsA significantly inhibited the cell migration ability of CaSki and HeLa cells in a wound-healing assay. Furthermore, Lut combined with AsA induced Apoptosis and inhibited migration through downregulated PI3K/Akt (PI3K, Akt and p70S6K), JNK/p38 MAPK and FAK (Integrin β1, paxillin and FAK) signaling and upregulated ERK signaling. In an in vivo study, Lut combined with AsA markedly inhibited cervical Cancer cell-derived xenograft tumor growth. Collectively, the present study showed that Lut combined with AsA may be used as an Anticancer agent to improve the prognosis of cervical Cancer. Indeed, with additional research to develop standardized dosages, Lut and AsA combination therapy could also be applied in clinical medicine.

Keywords

JNK/p38/ERK; PI3K/AKT/p70S6K; asiatic acid; cervical cancer; integrin β1/paxillin/FAK; luteolin.

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