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Review
. 2023 Apr 6:11:1164477.
doi: 10.3389/fchem.2023.1164477. eCollection 2023.

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Parteek Prasher  1 , Mousmee Sharma  2 , Sachin Kumar Singh  3   4 , Monica Gulati  3   4 , Dinesh Kumar Chellappan  5 , Rashi Rajput  4   6 , Gaurav Gupta  7   8 , Alibek Ydyrys  9 , Marzhan Kulbayeva  10 , Ahmad Faizal Abdull Razis  11   12 , Babagana Modu  12   13 , Javad Sharifi-Rad  14 , Kamal Dua  4   6
Affiliations
Review

Spermidine as a promising anticancer agent: Recent advances and newer insights on its molecular mechanisms

Parteek Prasher et al. Front Chem. .

Abstract

Spermidine is a naturally occurring polyamine compound found in semen. It is also found in several plant sources and boasts a remarkable biological profile, particularly with regards to its anticancer properties. Spermidine specifically interferes with the tumour cell cycle, resulting in the inhibition of tumor cell proliferation and suppression of tumor growth. Moreover, it also triggers autophagy by regulating key oncologic pathways. The increased intake of polyamines, such as spermidine, can suppress oncogenesis and slow the growth of tumors due to its role in anticancer immunosurveillance and regulation of polyamine metabolism. Spermidine/spermine N-1-acetyltransferase (SSAT) plays a critical role in polyamine homeostasis and serves as a diagnostic marker in human cancers. Chemically modified derivatives of spermidine hold great potential for prognostic, diagnostic, and therapeutic applications against various malignancies. This review discusses in detail the recent findings that support the anticancer mechanisms of spermidine and its molecular physiology.

Keywords: anticancer immunosurveillance; anticancer properties; cell proliferation; diagnostic marker; polyamines; spermidine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Mechanism of spermidine-induced autophagy. Abbreviations: FOXO: Fork-head transcription factors of the O class; Akt, Ak strain transforming; BNIP3, BCL2/adenovirus E1B 19 kDa protein-interacting protein 3; Ac, acylated; P, phosphorylated; HAT, histone acetyltransferase; EP300, E1A-associated protein p300; αtat1, α-tubulin acetyltransferase; CTSL, cathepsin L; ATG, autophagy related gene.
FIGURE 2
FIGURE 2
Mechanism of apoptosis induction by spermidine. Abbreviations: ROS, reactive oxygen species; Bax, Bcl-2 associated X protein; DR4, death receptor 4.
FIGURE 3
FIGURE 3
Synthesis of active acyl spermidine derivatives that induce apoptosis in cancer cells.
FIGURE 4
FIGURE 4
Bis-naphthalimido derivative of spermidine that indices apoptosis in adenocarcinoma cell lines.
FIGURE 5
FIGURE 5
Structure of N 1 , N 11 -diethylnorspermine that shows synergistic killing of colon carcinoma cells in combination with 5-fluorouracil.
FIGURE 6
FIGURE 6
Structure of apoptosis inducing α-methylspermidine (α-MeSpd) and N 1 , N 12 -dimethylspermine (Me2Spm).
FIGURE 7
FIGURE 7
Mechanism of polyamine metabolism and the role of SSAT. Abbreviations: AdoMet, S-Adenosylmethionine; MTA, Metastasis associated protein; APAO, N1 acetylpolyamine oxidase; SSAT, Spermidine/spermine N1-acetyltransferase; ODC, Ornithine decarboxylase; SMO, smoothened receptor.
FIGURE 8
FIGURE 8
Structure of N 1 , N 12 -bis(ethyl) spermine that inhibits the cancer cell growth by regulating the proliferation of cancer cells.
See this image and copyright information in PMC

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