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EXCLI Journal 2009;8:155-181 ISSN 1611-2156
Received: June 29, 2009, accepted: July 27, 2009, published: August 03, 2009

Review article:
APOPTOSIS:
MOLECULAR MECHANISMS AND PATHOGENICITY
Rajesh P. Rastogi, Richa and Rajeshwar P. Sinha*
Laboratory of Photobiology and Molecular Microbiology, Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi-221005 India
* Correspondingauthor: Dr. R.P. Sinha, Laboratory of Photobiology and Molecular Microbiology, Centre of Advanced Study in Botany, Banaras Hindu University, Varanasi221005, India, Ph.: +91 542 2307147; Fax: + 91 542 2368174; e-mail: r.p.sinha@gmx.net
ABSTRACT
Apoptosis triggered by exogenous and endogenous stimuli such as ultraviolet radiation, oxidative stress, and genotoxic chemicals is a crucial phenomenonwithin biological systems.
DNA damage activates and stabilizes p53 in nucleus and cytoplasm and regulates other proteins that stimulate intrinsic and extrinsic apoptotic pathways. Apoptosis is morphologically
distinct from that of necrosis and both the phenomena depend on the types, developmental
stages, physiological environment of tissues and the nature of death signal. Malfunctioning ofapoptotic pathway may cause human diseases like cancer, neurodegenerative and autoimmune
disorders. Recently, potent apoptosis-inducing compounds associated with human health have
been recorded that prevent tumor promotion, progression, and the occurrence of cellular inflammatory responses. Certain photosensitizing drugs are being employed in photodynamic
therapy to induce apoptosis for thetreatment of cancer and non-cancerous cells. This review
emphasizes the molecular mechanisms of apoptosis, associated diseases and certain therapeutic agents implicated in the elimination of malignant cells.
Keywords: apoptosis, apoptosis-inducing drugs, caspase, necrosis, pathogenesis, photodynamic therapy, ultraviolet radiation
and is considered to be an imperative component of various processesincluding normal cell turnover, proper development and
functioning of the immune system, multiplication of mutated chromosomes, hormone-dependent atrophy, normal embryonic development, elimination of indisposed cells and maintenance of cell homeostasis (Reed & Tomaselli, 2000; Elmore,
2007). DNA damage and production of the
predominant lesions such as cyclobutane
pyrimidine dimers (CPDs), 6–4photoproducts (6–4PPs) and certain other lesions
(Sinha & Häder, 2002; Kumari et al., 2008)
as a result of UV radiation (UVR), ionizing
radiation (IR), oxidative stress, replication
or recombination errors as well as from en-

INTRODUCTION
In addition to cell-cycle arrest and repair machinery, the damaged cells, where
damage is beyond repair, may induce an
apoptotic (programmed cell death;PCD)
response that is highly cell-specific and is
the most common form of physiologic cell
death in multicellular forms. The concept of
PCD was first developed by plant biologists
in 1920s (Jones, 2001). In unicellular organisms the mechanisms of PCD is less understood in comparison to metazoan, however some workers assume it as unicellular
origin with a later adoption by multicellular
life(Ameisen, 2002). Apoptosis play an
essential role in survival of the organisms
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EXCLI Journal 2009;8:155-181 ISSN 1611-2156
Received: June 29, 2009, accepted: July 27, 2009, published: August 03, 2009

family, such as Puma, Noxa, Bim, Bid, Bik,
Bak, Bax, Apaf-1, Bmf, Hrk, Pag608, Drs,
Fas and Gadd45 (Vogelstein et al., 2000;
Vousden and Lu, 2002; Tian et al., 2007).
This diversefamily includes multidomain
pro-apoptotic (e. g. Bax, Bak), anti-a programmed cell death (PCD apoptotic (e. g.
Bcl-2, Bcl-XL, Mcl-1) as well as a number
of BH3 only (e. g. Puma, Noxa, Bid, etc.)
proteins that together regulate mitochondrial permeability (Cory & Adams, 2002).
However, the relevance of transcriptional
activation in p53 apoptosis in human cancer
is highly controversial....