Pinocembrin as a novel anti-cancer agent: Exploring preclinical evidence along with therapeutic potential

Table 2 Preclinical evidence of pinocembrin’s anti-cancer activity by cancer type

Cancer type	Ref.	Model	Study type	Key findings
Breast cancer	Kumar et al[40], 2007	MCF-7, MDA-MB-231, SKBR3 cells; MCF-7 subcutaneous xenograft (mice)	In vitro and in vivo	PB induced G2/M cell-cycle arrest and apoptosis in MCF-7, MDA-MB-231, and SKBR3 cells by downregulating cyclin B1, Cdc2, PARP1, Bcl-2, and survivin, while upregulating cleaved PARP1, cleaved caspase-3/caspase-9, and Bax. In mice, oral PB suppressed MCF-7 tumor growth without overt toxicity, correlating with PI3K/AKT pathway inhibition
Colorectal cancer	León-González et al[66], 2014	HT-29 and HCT-116 cells	In vitro	PB triggered Bax-dependent mitochondrial apoptosis, evidenced by cytochrome C release and caspase-9/caspase-3 activation. It suppressed proliferation and survival signaling in colon cancer cells
Colorectal cancer	Jiang et al[64], 2022	HCT116, HT29 cells; HCT116 xenograft (mice)	In vitro and in vivo	PB inhibited the proliferation, migration, and invasiveness of HCT116 and HT29 cells by downregulating MMP-2 and N-cadherin and upregulating E-cadherin via LACTB modulation. In HCT116 xenografts, oral PB reduced tumor volume and metastasis
Melanoma	Zheng et al[68], 2018	A375 and B16F10 cells; B16F10 syngeneic mouse model (mice)	In vitro and in vivo	PB inhibited proliferation of A375 and B16F10 cells via endoplasmic reticulum stress (IRE1α/Xbp1) and caspase-12/caspase-4-mediated apoptosis and suppressed autophagy through PI3K/AKT/mTOR activation. In B16F10-bearing mice, oral PB (20 mg/kg) reduced tumor growth and induced apoptosis
Ovarian cancer	Gao et al[51], 2019	SKOV3 and OVCAR-3 cells	In vitro	PB inhibited proliferation (IC50 approximately 60 µM), migration, and invasion of SKOV3 and OVCAR-3 cells by downregulating PI3K/AKT signaling (reduced p-AKT, p-mTOR) and MMP-9, while promoting apoptosis (increased cleaved caspase-3 and Bax/Bcl-2 ratio)
Prostate cancer	Shao et al[65], 2021	PC-3 cells	In vitro	PB inhibited PC-3 proliferation and colony formation in a dose-dependent manner, induced G0/G1 cell-cycle arrest, increased reactive oxygen species production, and promoted apoptosis via regulation of caspase-3/caspase-9, Bax, and Bcl-2
Lung cancer	Gong[41], 2021	A549 cells	In vitro	PB suppressed A549 proliferation (25-200 µM) by restraining autophagy (reduced Beclin-1, light chain 3-II), enhanced apoptosis (increased caspase-3 activity), and reduced colony formation. Autophagy activator (rapamycin) reversed these effects, confirming Pino’s anti-proliferative, anti-autophagic, and pro-apoptotic roles
HCC	Saengboonmee et al[54], 2024	HepG2 and Li-7 cells	In vitro	PB caused G1 arrest in HepG2 and Li-7 cells by downregulating cyclin D1, cyclin E, CDK4, and CDK6; higher doses induced apoptosis (increased sub-G1). It suppressed STAT3 phosphorylation (Tyr705/Ser727), leading to decreased expression of downstream anti-apoptotic genes
HCC	Kurma et al[67], 2021	Rat DEN-induced hepatocarcinogenesis model; colon cancer xenograft (rats)	In vivo	PB neither inhibited nor prevented DEN-induced GST-P foci formation in rat liver; high doses (10 mg/kg) slightly increased GST-P foci, indicating no chemopreventive effect and potential promotion of preneoplastic lesions

AKT: Protein kinase B; CDK: Cyclin-dependent kinase; DEN: Diethylnitrosamine; GST-P: Glutathione S-transferase P; HCC: Hepatocellular carcinoma; MMP: Matrix metalloproteinase; mTOR: Mammalian target of rapamycin; PARP: Polyadenosine-diphosphate-ribose polymerase; PB: Pinocembrin; PI3K: Phosphoinositol-3 kinase.